Risk Stratification of Patients With Type 2 Long‐QT Syndrome Through Analysis of T‐Wave Morphology

Background Risk stratification in type 2 long‐QT syndrome remains challenging, as QT duration may not fully reflect all underlying arrhythmic vulnerability. We assessed whether an index derived from the T‐wave morphology is associated with cardiac events in a cohort with type 2 long‐QT syndrome. Methods We retrospectively and prospectively analyzed 54 genotype‐confirmed patients with type 2 long‐QT syndrome. T‐wave morphology in 8 independent leads was assessed using a warping‐based index, the T‐wave morphology variation (TMV) index, quantifying T‐wave morphologic changes from a general population‐based reference T‐wave. Association with the first lifetime occurrence of a cardiac event, including either syncope or the combined ventricular arrhythmia end point, was tested using univariate and multivariable Cox regression models. Results Using the 25th‐percentile threshold (TMV≤−18.41 ms), more negative TMV values indicating greater morphologic changes and a broader or delayed repolarization phase in the T‐wave signal relative to the control, as observed in lead I, were significantly associated with increased risk of cardiac event (hazard ratio [HR], 3.505 [95% CI, 1.673–7.341]; P <0.001). The association remained significant after adjustment for corrected QT (HR, 2.92 [95% CI, 1.111–7.676]; P =0.03) and after additional adjustment for sex (HR, 3.375 [95% CI, 1.256–9.067]; P =0.016), and the T‐wave morphology combination score (HR, 4.061 [95% CI, 1.369–12.046]; P =0.012). Conclusions T‐wave morphology abnormalities, quantified using TMV , are associated with a higher risk of cardiac event s after adjustment for corrected QT prolongation, sex, and morphology combination score. TMV could complement current risk stratification strategies, although confirmatory validation in larger, independent, prospective cohorts is pending.